Peruzzo 2016 Abstract Mito Xmas Meeting Innsbruck
| Novel psoralen-derivatives with increased solubility in cancer treatment. |
Link:
Peruzzo R, Azzolini M, Romio M, Manago A, Becker K, Mattarei A, Zoratti M, Gulbins E, Paradisi C, Leanza L, Szabo I (2016)
Event: Mito Xmas Meeting 2016 Innsbruck AT
Ion channels are emerging as new oncological targets. Indeed, several ion channels show a different expression pattern in normal and cancer cells. The potassium channel Kv1.3 has a multiple sub-cellular localization, including both in the plasma membrane and in the inner mitochondrial membrane.
Pharmacological inhibition of the mitochondrial channel (mtKv1.3), but not of the plasma membrane channel, by membrane permeant blockers, Psora-4, PAP-1 and clofazimine, triggered apoptosis in different cancer cells. Cell death occured even in the absence of Bax and Bak, by inducing mitochondrial membrane depolarization, production of mitochondrial ROS and release of cytochrome c. Downregulation by siRNA of Kv1.3 prevented all these effects, indicating specificity. Since membrane permeant Kv1.3 inhibitors are characterized by poor water solubility, in order to increase their bioavailability as well as their solubility, we have recently synthesized a few more soluble PAP-1 derivatives. The new derivatives have been found to selectively kill cancer cells in vitro and even in vivo in a mouse melanoma preclinical model, without inducing any side effect.
Labels: Pathology: Cancer
Event: Poster
Affiliations
- Peruzzo R(1), Azzolini M(2,3), Romio M(4), Managò A(1), Becker K(5), Mattarei A(4), Zoratti M(2,3), Gulbins E(5), Paradisi C(4), Leanza L(1), Szabò I(1,2)
- Dept Biology, Univ Padua, Italy
- CNR Inst Neurosciences, Padua, Italy
- Dept Biomedical Sc, Univ Padua, Italy
- Dept Chemical Sc, Univ Padua, Italy
- Dept Molecular Biology, Univ Duisburg-Essen, Germany
